Skip Navigation



ToxSci Advance Access published online on September 19, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl113
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow Supplementary Data
Right arrow All Versions of this Article:
94/2/281    most recent
kfl113v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by van der Ven, L. T. M.
Right arrow Articles by Vos, J. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van der Ven, L. T. M.
Right arrow Articles by Vos, J. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 14, 2006
Accepted September 13, 2006

Endocrine Toxicology

A 28-Day Oral Dose Toxicity Study Enhanced to Detect Endocrine Effects of Hexabromocyclododecane (HBCD) in Wistar Rats

Leo T. M. van der Ven 1 *, Aart Verhoef 1, Ton van de Kuil 1, Wout Slob 2, Pim E. G. Leonards 3, Theo J. Visser 4, Timo Hamers 3, Maria Herlin 5, Helen Håkansson 5, Hanna Olausson 5, Aldert H. Piersma 1, and Josephus G. Vos 1

1 Laboratory for Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, the Netherlands
2 Centre for Substances and Integrated Risk Assessment, National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, the Netherlands
3 Institute for Environmental Studies, Vrije Universiteit Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands
4 Department of Internal Medicine, Room Ee 502, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands
5 The Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden

* To whom correspondence should be addressed.
Leo T. M. van der Ven, E-mail: L.van.der.ven{at}rivm.nl


  Abstract

A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response analysis with calculation of a benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CES) of 10-20%. The most remarkable findings were dose-related effects on the thyroid hormone axis, i.e. decreased total thyroxin (TT4, BMDL 55.5 mkd at CES -10%), increased pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the pituitary, increased thyroid weight (1.6 mkd at 10%) and thyroid follicle cell activation. These effects were restricted to females. Female rats also showed increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl transferase (4.1 mkd at 10%), suggesting that aberrant metabolisation of T4 triggers feed-back activation of the TH system. These effects were accompanied by possibly secondary effects, including increased cholesterol (7.4 mkd at 10%), increased tibial bone mineral density (>49 mkd at 10%), both in females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in males). Overall, female rats appeared to be more sensitive to HBCD than male rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the thyroid weight, which was the most sensitive parameter in the sequence of events.

Keywords: hexabromocyclododecane; brominated flame retardants; endocrine disruption; thyroid hormones; rats; hazard identification; risk assessment.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.